ZFIN ID: ZDB-PUB-091101-11
Meis cofactors control HDAC and CBP accessibility at Hox-regulated promoters during zebrafish embryogenesis
Choe, S.K., Lu, P., Nakamura, M., Lee, J., and Sagerström, C.G.
Date: 2009
Source: Developmental Cell   17(4): 561-567 (Journal)
Registered Authors: Choe, Seong-Kyu, Nakamura, Mako, Sagerström, Charles
Keywords: DEVBIO
MeSH Terms:
  • Acetylation
  • Animals
  • Blotting, Western
  • CREB-Binding Protein/genetics
  • CREB-Binding Protein/metabolism*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Embryo, Nonmammalian/physiology*
  • Embryonic Development
  • Gene Expression Regulation, Developmental*
  • Histone Deacetylase 1
  • Histone Deacetylases/genetics*
  • Histone Deacetylases/metabolism
  • Histones/metabolism
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Immunoprecipitation
  • Luciferases/metabolism
  • Promoter Regions, Genetic/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Regulatory Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 19853569 Full text @ Dev. Cell
Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.